An intensive effort was directed toward studying the prevention and treatment of opportunistic infections associated with AIDS. Phase I/II trials of BW566C80 as salvage therapy for cerebral toxoplasmosis demonstrated both long-term safety and efficacy. BW566C80 in combination with pyrimethamine has also proven safe and effective. Azithromycin as salvage therapy for toxoplasmosis resulted in early treatment failures. In data from a trial of foscarnet for the treatment of cytomegalovirus retinitis, higher titers of neutralizing antibody were found to correlate with a longer recurrence-free time on therapy. Thus, a Phase I/II study of the pharmacokinetics of CMVIG-IV for the prevention of CMV disease in patients with AIDS was begun. Data from this study will be used in a planned Phase II efficacy study of this product. Analysis of a multi-center Phase III trial of BW566C80 vs. trimethoprim-sulfamethoxazole for the treatment of pneumocystis pneumonia demonstrated equivalent overall therapeutic efficacy but therapeutic superiority of TMP-SMX with superior safety and tolerability of BW566C80. A study of the pharmacokinetics of BW566C80 confirmed the limited oral absorption of this agent with a plateau of absorption, large inter-patient variability, and drug levels that may be suboptimal for the treatment or prevention of pneumocystis pneumonia in some patients. A pilot study of weekly dapsone and dapsone plus pyrimethamine for the prevention of pneumocystis pneumonia demonstrated the safety of these regimens but also a significant occurrence of break-through episodes of pneumonia. A seven-arm Phase I/II trial of sparfloxacin, azithromycin alone or in combination plus a salvage regimen using these agents with ethambutol and clofazimine for the treatment of Mycobacterium avium complex infection is now ready to enroll. A controlled trial of BW566C80 for the treatment of cryptosporidiosis and microsporidiosis has been substantially completed but has yet to be analyzed.